What are the common toxicities of Olaparib (poly (ADP-ribose) polymerase (PARP) inhibitor) in landmark trials?

Olaparib Toxicity Profile in Landmark Trials

Anemia is the most common and clinically significant grade ≥3 toxicity with olaparib, occurring in 5-22% of patients across landmark trials, followed by fatigue/asthenia, nausea, and vomiting which are typically lower grade and less frequent. 1

Hematologic Toxicities

Anemia

• Grade ≥3 anemia occurs in 5-22% of patients receiving olaparib monotherapy 1
• When combined with bevacizumab, grade ≥3 anemia occurs in 17% of patients 1
• In prostate cancer trials (PROfound), all-grade anemia occurred in 50% of patients, though mostly grade 1-2 2
• Anemia is the most common dose-limiting toxicity requiring transfusion support, dose interruptions, or reductions 3, 4
• Any-grade anemia ranges from 39-41% in ovarian cancer maintenance trials 1

Neutropenia and Thrombocytopenia

• Grade ≥3 neutropenia occurs in 9% of olaparib-treated patients 1
• Any-grade neutropenia occurs in 23% of patients 1
• Grade ≥3 thrombocytopenia is rare with olaparib monotherapy (1-2%) 1
• Olaparib causes significantly less neutropenia and thrombocytopenia compared to niraparib (which has 19.6% grade ≥3 neutropenia and 34% grade ≥3 thrombocytopenia) 1

Non-Hematologic Toxicities

Gastrointestinal Effects

• Nausea occurs in 43-77% of patients (any grade), but grade ≥3 nausea is rare (<5%) 1, 2
• Vomiting occurs in 40% of patients (any grade), with grade ≥3 in approximately 1% 1
• These gastrointestinal symptoms typically peak within the first 2 months of treatment 2

Fatigue/Asthenia

• Fatigue/asthenia occurs in 42-63% of patients (any grade) 1, 2
• Grade ≥3 fatigue is uncommon with olaparib monotherapy (approximately 4%) 1
• This contrasts with rucaparib, where grade 3/4 fatigue occurs in 26.2% of patients 1

Other Common Toxicities

• Decreased appetite occurs in 31% of patients 2
• Constipation occurs in 28% of patients 1
• Diarrhea and dysgeusia are less common 1

Rare but Serious Toxicities

Myelodysplastic Syndrome/Acute Myeloid Leukemia

• MDS/AML occurs in ≤2% of patients across trials 1
• This risk is mentioned in FDA labeling and requires long-term monitoring 1

Venous Thromboembolic Events

• Venous thromboembolic events occur in 8% of olaparib-treated patients 2
• Pulmonary emboli are specifically noted as rare but serious adverse effects 1

Pneumonitis

• Drug-induced pneumonitis occurs in approximately 2% of patients 1
• This is a rare but potentially serious complication requiring clinical vigilance 1

Treatment Discontinuation and Dose Modifications

• Overall discontinuation due to adverse events occurs in 11.5-12% of patients with olaparib monotherapy 1
• When combined with bevacizumab, discontinuation rates increase to 20% 1
• Hematologic toxicities are the most common cause of dose reductions and treatment discontinuation 1
• Most adverse events are managed successfully with dose interruptions and reductions without requiring permanent discontinuation 1

Quality of Life Impact

• Despite the toxicity profile, olaparib does not negatively impact health-related quality of life compared to placebo 1
• Quality of life scores remain comparable between treatment groups throughout maintenance therapy 1
• The absence of disease-related symptoms during maintenance therapy helps maintain overall quality of life despite treatment-related adverse events 1

Clinical Management Pearls

• Hematologic toxicities typically peak within the first 2 months of treatment 2
• Complete blood count monitoring is mandatory throughout treatment 1, 3
• Type and screen availability with transfusion support readiness is required 1, 3
• Most adverse events are grade 1-2 and do not require treatment interruption 4
• The majority of toxicities can be managed with appropriate dose reductions and delays, allowing patients to continue deriving clinical benefit 1